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A Study of the Efficacy of Canakinumab in Prevention of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy (Core Study) and a Long-term Study of the Efficacy and Safety of Canakinumab in Patients With Gout (Extension Study)

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ClinicalTrials.gov Identifier: NCT00819585
Recruitment Status : Completed
First Posted : January 9, 2009
Results First Posted : May 6, 2011
Last Update Posted : July 17, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 8, 2009
First Posted Date  ICMJE January 9, 2009
Results First Submitted Date  ICMJE February 28, 2011
Results First Posted Date  ICMJE May 6, 2011
Last Update Posted Date July 17, 2018
Study Start Date  ICMJE December 2008
Actual Primary Completion Date August 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2018)
Core Study: Mean Number of Gout Flares Per Participant [ Time Frame: Baseline of the core study to Week 16 ]
A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.
Original Primary Outcome Measures  ICMJE
 (submitted: January 8, 2009)
To determine the target dose of canakinumab that leads to at least comparable efficacy as colchicine with respect to the mean number of gout flares occurring during 16 weeks after randomization. [ Time Frame: 16 weeks ]
Change History Complete list of historical versions of study NCT00819585 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2018)
  • Core Study: Mean Number of Gout Flares for the Repeat Dose Regimen of Canakinumab as Compared to the Single Doses of Canakinumab [ Time Frame: up to 16 weeks after randomization ]
  • Core Study: Percentage of Participants With at Least 1 Gout Flare Within 16 Weeks After Randomization [ Time Frame: Baseline of the core study to Week 16 ]
    The percentage of participants experiencing at least 1 gout flare within 16 weeks after randomization. A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.
  • Core Study: Percentage of Participants With Gout Flare at Different Time Points [ Time Frame: Days 2, 4, 6, and Weeks 2, 4, 6, 10, and 16 of the core study ]
    A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.
  • Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares [ Time Frame: Baseline of the core study to Week 16 ]
    Participants rated the intensity of pain in the most affected joint on a 0-100 mm visual analog scale, which ranged from no pain (left end, 0) to unbearable pain (right end, 100). Participants assessed pain intensity on the day of onset of the gout flare and in the morning of the 6 following days.
  • Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares [ Time Frame: Baseline of the core study to Week 16 ]
    Participants assessed the intensity of pain in the most affected joint on a 5-point Likert scale, which ranged from 1 to 5 (1=None, 2=Mild, 3=Moderate, 4=Severe, 5=Extreme). Participants assessed pain intensity on the day of onset of the gout flare and in the morning of the 6 following days.
  • Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale [ Time Frame: Days 15, 29, 57, 85, 113, and 141 of the core study ]
    The study physician made a global assessment of the participant's response to treatment on a 5-point Likert scale (Very good, Good, Fair, Poor, Very poor) at Days 15, 29, 57, 85, 113, and 141. The category 'Not assessed' includes missing data and 'not done'. The number of participants in each of the 5 categories of the Likert scale are reported.
  • Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare [ Time Frame: Baseline of the extension study until 7 days after the onset of the first gout flare (up to 24 weeks) ]
    Participant's rated the intensity of pain in the most affected joint during the first flare on a 0-100 mm visual analog scale, which ranged from no pain (left end, 0) to unbearable pain (right end, 100). Assessments were made pre-dose and 24 hours, 3 days, 4 days, and an average of 5-7 days post-dose
  • Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale [ Time Frame: Baseline of the extension study until the end of the study (up to 24 weeks) ]
    Study participants made a global assessment of their response to treatment on a 5-point Likert scale (Excellent, Good, Acceptable, Slight, Poor) at the control visit 7±2 days following each of their first 3 flares. The number of participants in each of the 5 categories of the Likert scale are reported.
  • Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale [ Time Frame: Baseline of the extension study until the end of the study (up to 24 weeks) ]
    The study physician made a global assessment of the participant's response to treatment on a 5-point Likert scale (Very good, Good, Fair, Poor, Very poor) at the control visit 7±2 days following each of the first 3 flares. The category 'Not assessed' includes missing data and 'not done'. The number of participants in each of the 5 categories of the Likert scale are reported.
  • Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare [ Time Frame: Baseline of the extension study until the end of the study (up to 24 weeks) ]
    Tenderness was rated on a 0-3 point scale: 0="no pain", 1=patient states that "there is pain", 2=patient states "there is pain and winces", and 3=patient states "there is pain, winces and withdraws" on palpation or passive movement of the most affected joint. Swelling was rated on a 0-3 point scale: 0="no swelling", 1="palpable", 2="visible", and 3=bulging beyond the joint margins". Erythema was rated as present, absent, or not assessable. Assessments were performed at the flare and control visits.
  • Extension Study: Amount of Rescue Medication Taken [ Time Frame: Baseline of the extension study until the end of the study (up to 24 weeks) ]
    The amount of naproxen and prednisolone taken after receiving treatment for each of the first 3 flares was recorded.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2009)
  • To evaluate the efficacy of a repeat dose regimen of canakinumab as compared to the single doses of canakinumab with regards to the mean number of gout flares up to 16 weeks after randomization [ Time Frame: 16 weeks ]
  • To evaluate the number of patients with gout flares with canakinumab as compared to colchicine up to 16 weeks after randomization [ Time Frame: 16 weeks ]
  • To evaluate the time to first gout flare with canakimunab as compared to colchicine up to 16 weeks after randomization [ Time Frame: 16 weeks ]
  • To evaluate Patient's global pain intensity on a 0-100 mm VAS and 5-point Likert scale during gout flares with canakinumab as compared to colchicine up to 16 weeks after randomization [ Time Frame: 16 weeks ]
  • To evaluate the efficacy of canakinumab as compared to colchicine with regards to the Physician's global assessment of response to therapy on a 5-point Likert scale up to 16 weeks after randomization [ Time Frame: 16 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Efficacy of Canakinumab in Prevention of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy (Core Study) and a Long-term Study of the Efficacy and Safety of Canakinumab in Patients With Gout (Extension Study)
Official Title  ICMJE A 24-week, Dose-ranging, Multicenter, Double-blind, Double-dummy, Active-controlled Core Study to Evaluate Canakinumab for Prophylaxis of Signs and Symptoms of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy and a 24-week Open-label, Multicenter Extension Study to Assess Safety, Tolerability and Efficacy of Canakinumab in Patients With Gout Who Are Given Canakinumab at the Time of Gout Flare
Brief Summary The 24-week, dose-ranging, multi-center, double-blind, double-dummy, active-controlled core study investigated the prophylactic effect of canakinumab on the signs and symptoms of acute flares in chronic gout patients initiating allopurinol therapy. The core study was followed by a 24-week open-label, multicenter extension study to assess the safety, tolerability, and efficacy of canakinumab in patients with gout who were given canakinumab at the time of gout flare.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Gout
Intervention  ICMJE
  • Drug: Canakinumab
    Canakinumab was supplied in glass vials as a lyophilized powder.
  • Drug: Colchicine
    0.5 mg capsule orally once daily for 16 weeks.
  • Drug: Allopurinol
    100-300 mg orally once daily for 24 weeks.
  • Drug: Placebo Matching Canakinumab
    Subcutaneous injection.
  • Drug: Placebo Matching Colchicine
    Capsule orally once daily for 16 weeks.
Study Arms  ICMJE
  • Experimental: Core study: Canakinumab 25 mg
    Canakinumab 25 mg subcutaneously (sc) once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.
    Interventions:
    • Drug: Canakinumab
    • Drug: Allopurinol
    • Drug: Placebo Matching Canakinumab
    • Drug: Placebo Matching Colchicine
  • Experimental: Core study: Canakinumab 50 mg
    Canakinumab 50 mg sc once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.
    Interventions:
    • Drug: Canakinumab
    • Drug: Allopurinol
    • Drug: Placebo Matching Canakinumab
    • Drug: Placebo Matching Colchicine
  • Experimental: Core study: Canakinumab 100 mg
    Canakinumab 100 mg sc once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.
    Interventions:
    • Drug: Canakinumab
    • Drug: Allopurinol
    • Drug: Placebo Matching Canakinumab
    • Drug: Placebo Matching Colchicine
  • Experimental: Core study: Canakinumab 200 mg
    Canakinumab 100 mg sc once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.
    Interventions:
    • Drug: Canakinumab
    • Drug: Allopurinol
    • Drug: Placebo Matching Canakinumab
    • Drug: Placebo Matching Colchicine
  • Experimental: Core study: Canakinumab 300 mg
    Canakinumab 300 mg sc once at Day 1, placebo sc at Days 29, 57, and 85 plus daily placebo capsules for 16 weeks. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.
    Interventions:
    • Drug: Canakinumab
    • Drug: Allopurinol
    • Drug: Placebo Matching Canakinumab
    • Drug: Placebo Matching Colchicine
  • Experimental: Core study: Canakinumab q4wk
    Canakinumab 50 mg sc at Days 1, and 29 followed by canakinumab 25 mg sc on Days 57, and 85 plus daily placebo capsules for 16 weeks, repeated every 4 week (q4wk). Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.
    Interventions:
    • Drug: Canakinumab
    • Drug: Allopurinol
    • Drug: Placebo Matching Colchicine
  • Active Comparator: Core study: Colchicine 0.5 mg
    Colchicine 0.5 mg capsule orally once daily throughout the whole treatment phase of 16 weeks plus placebo matching canakinumab s.c. at Days 1, 29, 57, and 85. Allopurinol treatment was initiated at the latest at baseline (Visit 2) according to the patient's renal function / estimated creatinine clearance at screening (Visit 1). Allopurinol was administered orally to all randomized patients once daily (100 mg-300 mg) for 24 weeks.
    Interventions:
    • Drug: Colchicine
    • Drug: Allopurinol
    • Drug: Placebo Matching Canakinumab
  • Experimental: Extension study: Group A
    Participants who were randomized to canakinumab in the core study and were treated with canakinumab for at least 1 flare in the extension study.
    Intervention: Drug: Canakinumab
  • Experimental: Extension study: Group B
    Patients who were randomized to canakinumab in the core study but did not receive treatment with canakinumab in the extension study.
    Intervention: Drug: Canakinumab
  • Experimental: Extension study: Group C
    Patients who were randomized to colchicine in the core study and were treated with canakinumab for at least 1 flare in the extension study.
    Interventions:
    • Drug: Canakinumab
    • Drug: Colchicine
  • Experimental: Extension study: Group D
    Patients who were randomized to colchicine in the core study but did not receive treatment with canakinumab in the extension study.
    Intervention: Drug: Colchicine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 12, 2011)
432
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2009)
440
Actual Study Completion Date  ICMJE August 2010
Actual Primary Completion Date August 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Core study

Inclusion Criteria:

  • Signed written informed consent before any study procedure is performed.
  • History of at least 2 gout flares in the year prior to Screening (Visit 1, based on patient history), thus, candidates for initiating uric acid lowering therapy.
  • Confirmed diagnosis of gout meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of arthritis of primary gout.
  • Body Mass Index (BMI) ≤ 40 kg/m^2.
  • Willingness to initiate allopurinol therapy as urate lowering agent for their gout therapy or having initiated allopurinol therapy within ≤ 1 month before Screening (Visit 1) or willing to re-initiate allopurinol therapy if this was stopped > 2 months before Screening (Visit 1) for reasons different to toxicity/ intolerance or lack of efficacy.

Exclusion Criteria:

  • Acute gout flare within 2 weeks of Screening (Visit 1) and during the Screening period.
  • History of allergy or contraindication to colchicine or allopurinol.
  • History of intolerance to allopurinol or to oral colchicine in appropriate dose for prophylactic use.
  • History of bone marrow suppression.
  • Absolute or relative contraindication to both naproxen and oral prednisolone/ prednisone.

Extension study

Inclusion criteria:

  • Patients who completed the core study. A patient is defined as completing the core study if he/she completed the study up to and including the last visit (Visit 9).
  • Patients who have signed a written informed consent before any trial procedure is performed.

Exclusion Criteria:

  • Patients for whom continuation in the extension study is not considered appropriate by the treating physician.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive pregnancy test (serum or urine).

Other protocol-defined inclusion/exclusion criteria applied to the study.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Belgium,   Colombia,   Czechia,   Germany,   Guatemala,   Hungary,   Poland,   Portugal,   Russian Federation,   Singapore,   Slovakia,   South Africa,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT00819585
Other Study ID Numbers  ICMJE CACZ885H2251
EudraCT : 2008-005876-28
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP